Ⅲ~ⅣA期食管鳞状细胞癌放化疗后行巩固化疗的疗效:一项真实世界临床研究

Efficacy of consolidation chemotherapy after radical radiotherapy and chemotherapy for stage Ⅲ-ⅣA esophageal squamous cell carcinoma: a real-world clinical study

目的探讨Ⅲ~ⅣA期食管鳞状细胞癌(ESCC)患者放化疗后行巩固化疗在真实世界的疗效。方法回顾性分析2018年1月1日至2022年12月31日中国科学院合肥肿瘤医院收治的139例Ⅲ~ⅣA期行放化疗ESCC患者的临床资料。根据患者放化疗后是否行巩固化疗, 将患者分为对照组(n=85)和巩固化疗组(n=54)。比较两组客观缓解率(ORR)、疾病控制率(DCR)、无进展生存期(PFS)及总生存期(OS)。采用Kaplan-Meier法绘制生存曲线并行log-rank检验, 采用Cox比例风险模型行单因素和多因素分析。结果对照组、巩固化疗组ORR分别为44.71%(38/85)、66.67%(36/54), 差异有统计学意义(χ^(2)=5.54, P=0.018);DCR分别为70.59%(60/85)、87.04%(47/54), 差异有统计学意义(χ^(2)=5.04, P=0.025)。两组患者中位PFS分别为9.0、13.1个月, 差异有统计学意义(χ^(2)=12.74, P<0.001);中位OS分别为15.0、20.6个月, 差异有统计学意义(χ^(2)=24.75, P<0.001)。两组cT3-4N1-3M0亚组ESCC患者中位OS分别为16.0、30.8个月, 差异有统计学意义(χ^(2)=23.49, P<0.001)。单因素分析显示, 肿瘤长度(HR=1.57, 95%CI为1.04~2.36, P=0.032)、客观缓解(HR=0.08, 95%CI为0.04~0.17, P<0.001)、巩固化疗(HR=0.32, 95%CI为0.20~0.51, P<0.001)均是Ⅲ~ⅣA期行根治性放化疗后ESCC患者OS的影响因素。多因素分析显示, 肿瘤长度(HR=1.59, 95%CI为1.05~2.43, P=0.030)、客观缓解(HR=0.05, 95%CI为0.02~0.10, P<0.001)、巩固化疗(HR=0.22, 95%CI为0.13~0.36, P<0.001)均是Ⅲ~ⅣA期行放化疗后ESCC患者OS的独立影响因素。安全性方面, 巩固化疗组发生7例不良反应, 主要有消化道反应、白细胞降低, 其中1~2级5例、3~4级2例;对照组发生22例不良反应, 主要有中性粒细胞减少、血小板减少、贫血、消化道反应, 其中1~2级16例, 3~4级6例。两组不良反应总发生率分别为12.96%(7/54)、25.88%(22/85), 差异无统计学意义(χ^(2)=3.34, P=0.068)。结论Ⅲ~ⅣA期ESCC患者放化疗后行巩固化疗可显著改善预后, 且总体不良反应可控。

Objective To explore the efficacy of consolidation chemotherapy after radical radiotherapy and chemotherapy in stageⅢ-ⅣA esophageal squamous cell carcinoma(ESCC)patients in the real world.Methods The clinical data of 139 patients with stageⅢ-ⅣA ESCC who underwent radical radiotherapy and chemotherapy from January 1,2018 to December 31,2022 in Hefei Cancer Hospital,Chinese Academy of Sciences were retrospectively analyzed.Patients were divided into a control group(n=85)and a consolidation chemotherapy group(n=54)based on whether they underwent consolidation chemotherapy after radical radiotherapy and chemotherapy.The objective response rate(ORR),disease control rate(DCR),progression-free survival(PFS),and overall survival(OS)between the two groups were compared.The Kaplan-Meier method was used to draw survival curves and log-rank tests were conducted.The Cox proportional risk model was used for univariate and multivariate analysis.Results The ORR of the control group and the consolidation chemotherapy group were 44.71%(38/85)and 66.67%(36/54),respectively,with a statistically significant difference(χ^(2)=5.54,P=0.018);the DCR were 70.59%(60/85)and 87.04%(47/54),respectively,with a statistically significant difference(χ^(2)=5.04,P=0.025).The median PFS of the two groups of patients were 9.0 and 13.1 months,respectively,with a statistically significant difference(χ^(2)=12.74,P<0.001);the median OS were 15.0 and 20.6 months,respectively,with a statistically significant difference(χ^(2)=24.75,P<0.001).The median OS of ESCC patients in two subgroups of cT3-4N1-3M0 were 16.0 and 30.8 months,respectively,with a statistically significant difference(χ^(2)=23.49,P<0.001).Univariate analysis showed that tumor length(HR=1.57,95%CI:1.04-2.36,P=0.032),objective response(HR=0.08,95%CI:0.04-0.17,P<0.001),and consolidation chemotherapy(HR=0.32,95%CI:0.20-0.51,P<0.001)were all influencing factors for OS in ESCC patients undergoing radical radiotherapy and chemotherapy in stagesⅢ-ⅣA.Multivariate analysis showed that tumor length(HR=1.59,95%CI:1.05-2.43,P=0.030),objective response(HR=0.05,95%CI:0.02-0.10,P<0.001),and consolidation chemotherapy(HR=0.22,95%CI:0.13-0.36,P<0.001)were all independent influencing factors for OS in stageⅢ-ⅣA ESCC patients undergoing radiotherapy and chemotherapy.In terms of safety,the consolidation chemotherapy group experienced 7 adverse reactions mainly gastrointestinal reaction and leukopenia,including 5 cases of grade 1-2 and 2 cases of grade 3-4;22 cases of adverse reactions occurred in the control group including 16 cases of grade 1-2 and 6 cases of grade 3-4 mainly including neutropenia,thrombocytopenia,anemia and digestive tract reaction.The incidence rates of adverse reactions in the two groups were 12.96%(7/54)and 25.88%(22/85),respectively,with no statistically significant difference(χ^(2)=3.34,P=0.068).Conclusion After radical radiotherapy and chemotherapy,consolidation chemotherapy can significantly improve the prognosis of stageⅢ-ⅣA ESCC patients,and the overall adverse reactions are controllable.